A Hepatic Network of Dendritic Cells Mediates CD4 T Cell Help Outside Lymphoid Organs

While CD4 T cells are a prerequisite for CD8 T cell-mediated protection against intracellular hepatotropic pathogens, the mechanisms facilitating the transfer of CD4-help to intrahepatic CD8 T cells are unknown. Here, we developed an experimental system to investigate cognate CD4 and CD8 T cell responses to a model-antigen expressed de novo in hepatocytes and reveal that after initial priming, effector CD4 and CD8 T cells migrate into portal tracts and peri-central vein regions of the liver where they cluster with type-1 conventional dendritic cells. These dendritic cells are locally licensed by CD4 T cells and expand the number of CD8 T cells in situ, resulting in larger effector and memory CD8 T cell pools. These findings reveal that CD4 T cells promote intrahepatic immunity by amplifying the CD8 T cell response via peripheral licensing of hepatic type-1 conventional dendritic cells and identify intrahepatic perivascular compartments specialized in facilitating effector T cell-dendritic cell interactions.